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弥漫性胶质瘤中miR-17-5p-CXCL14轴相关转录组图谱及临床结局

miR-17-5p-CXCL14 axis related transcriptome profile and clinical outcome in diffuse gliomas.

作者信息

Zeng Ailiang, Yin Jianxin, Wang Zheng, Zhang Chuanbao, Li Rui, Zhang Zhuoran, Yan Wei, You Yongping

机构信息

Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.

Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.

出版信息

Oncoimmunology. 2018 Sep 11;7(12):e1510277. doi: 10.1080/2162402X.2018.1510277. eCollection 2018.

Abstract

GBM tissues are comprised of not only tumor cells but also tumor-associated nontumor cells, such as stromal cells and immune cells, which dilute the purity of glioma cells and function in glioma biology. However, the roles of miRNAs in modulating glioma purity are not clarified. In total, 838 glioma samples with transcriptome data, including 537 RNAseq data from TCGA project and 301 microarray data from Chinese Glioma Genome Atlas (CGGA project), were recruited into our investigation. Tumor purity, molecular subtypes and IDH status were also available. R language was employed as the main tool for statistical analysis and graphical work. Screening miRNA profiling and paired TCGA samples' transcriptome data demonstrates that miR-17-5p expression harbors the most significant positive correlation with glioma purity among all miRNAs. CXCL14 shows robust negative correlation with miR-17-5p expression in TCGA and CGGA dataset. miR-17-5p directly targets CXCL14 and functions as a tumor-suppressor of GBM. CXCL14 showed lower expression in proneural subtype and may contribute as a potential marker for proneural subtype in glioma. Genes markedly correlated with CXCL14 are involved in essential functions associated with anti-tumor immune process. CXCL14 has a strong correlation with immune(T cells, Monocytic lineage and Neutrophils) and Fibroblasts within glioma environment. miR-17-5p and CXCL14 exhibited predictive values for high-grade glioma(HGG) patients: Higher miR-17-5p indicated significantly longer survival while lower CXCL14 indicated longer survival. Our results highlight the importance of the miR-17-5p-CXCL14 axis in regulating key steps of anti-tumor immune process and may serve as potential targets of immune treatments for gliomas.

摘要

胶质母细胞瘤(GBM)组织不仅由肿瘤细胞组成,还包含肿瘤相关的非肿瘤细胞,如基质细胞和免疫细胞,这些细胞会稀释胶质瘤细胞的纯度并在胶质瘤生物学中发挥作用。然而,微小RNA(miRNA)在调节胶质瘤纯度方面的作用尚未明确。本研究共纳入了838例具有转录组数据的胶质瘤样本,其中包括来自癌症基因组图谱(TCGA)项目的537例RNA测序数据和来自中国胶质瘤基因组图谱(CGGA项目)的301例微阵列数据。同时还获取了肿瘤纯度、分子亚型和异柠檬酸脱氢酶(IDH)状态等信息。R语言被用作统计分析和图形绘制的主要工具。筛选miRNA谱和配对的TCGA样本转录组数据表明,在所有miRNA中,miR-17-5p的表达与胶质瘤纯度具有最显著的正相关。在TCGA和CGGA数据集中,趋化因子配体14(CXCL14)与miR-17-5p的表达呈强烈负相关。miR-17-5p直接靶向CXCL14,并作为GBM的肿瘤抑制因子发挥作用。CXCL14在神经干细胞样亚型中表达较低,可能是胶质瘤神经干细胞样亚型的潜在标志物。与CXCL14显著相关的基因参与了与抗肿瘤免疫过程相关的重要功能。CXCL14与胶质瘤环境中的免疫细胞(T细胞、单核细胞系和中性粒细胞)和成纤维细胞密切相关。miR-17-5p和CXCL14对高级别胶质瘤(HGG)患者具有预测价值:miR-17-5p水平较高表明患者生存期显著延长,而CXCL14水平较低则表明生存期延长。我们的研究结果突出了miR-17-5p-CXCL14轴在调节抗肿瘤免疫过程关键步骤中的重要性,可能成为胶质瘤免疫治疗的潜在靶点。

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